Skin marker combined with surface-guided auto-positioning for breast DIBH radiotherapy daily initial patient setup: An optimal schedule for both accuracy and efficiency.

BACKGROUND AND PURPOSE: By employing three surface-guided radiotherapy (SGRT)-assisted positioning methods, we conducted a prospective study of patients undergoing SGRT-based deep inspiration breath-hold (DIBH) radiotherapy using a Sentine/Catalys system. The aim of this study was to optimize the initial positioning workflow of SGRT-DIBH radiotherapy for breast cancer. MATERIALS AND METHODS: A total of 124 patients were divided into three groups to conduct a prospective comparative study of the setup accuracy and efficiency for the daily initial setup of SGRT-DIBH breast radiotherapy. Group A was subjected to skin marker plus SGRT verification, Group B underwent SGRT optical feedback plus auto-positioning, and Group C was subjected to skin marker plus SGRT auto-positioning. We evaluated setup accuracy and efficiency using cone-beam computed tomography (CBCT) verification data and the total setup time. RESULTS: In groups A, B, and C, the mean and standard deviation of the translational setup-error vectors were small, with the highest values of the three directions observed in group A (2.4 ± 1.6, 2.9 ± 1.8, and 2.8 ± 2.1 mm). The rotational vectors in group B (1.8 ± 0.7°, 2.1 ± 0.8°, and 1.8 ± 0.7°) were significantly larger than those in groups A and C, and the Group C setup required the shortest amount of time, at 1.5 ± 0.3 min, while that of Group B took the longest time, at 2.6 ± 0.9 min. CONCLUSION: SGRT one-key calibration was found to be more suitable when followed by skin marker/tattoo and in-room laser positioning, establishing it as an optimal daily initial set-up protocol for breast DIBH radiotherapy. This modality also proved to be suitable for free-breathing breast cancer radiotherapy, and its widespread clinical use is recommended.

Lipid-mediated protein corona regulation with increased apolipoprotein A-I recruitment for glioma targeting.

Protein corona has long been a source of concern, as it might impair the targeting efficacy of targeted drug delivery systems. However, engineered up-regulating the adsorption of certain functional serum proteins could provide nanoparticles with specific targeting drug delivery capacity. Herein, apolipoprotein A-I absorption increased nanoparticles (SPC-PLGA NPs), composed with the Food and Drug Administration approved intravenously injectable soybean phosphatidylcholine (SPC) and poly (DL-lactide-co-glycolide) (PLGA), were fabricated for enhanced glioma targeting. Due to the high affinity of SPC and apolipoprotein A-I, the percentage of apolipoprotein A-I in the protein corona of SPC-PLGA NPs was 2.19-fold higher than that of nanoparticles without SPC, which made SPC-PLGA NPs have superior glioma targeting ability through binding to scavenger receptor class BI on blood-brain barrier and glioma cells both in vitro and in vivo. SPC-PLGA NPs loaded with paclitaxel could effectively reduce glioma invasion and prolong the survival time of glioma-bearing mice. In conclusion, we provided a good example of the direction of achieving targeting drug delivery based on protein corona regulation.

Variable phenotypes and outcomes associated with the MMACHC c.482G > A mutation: follow-up in a large CblC disease cohort.

BACKGROUND: The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene (MMACHC) c.482G > A mutation in 195 Chinese cases with CblC disease. METHODS: We carried out a national, retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G > A variant either in a homozygous or compound heterozygous state. The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G > A mutation. Clinical features, including disease onset, symptoms, biochemical metabolites, gene mutation, and follow-up outcomes were reviewed and analyzed in detail. The median follow-up period spanned 3 years and 8 months, with a range of 1 year and 2 months to 12 years and 10 months. RESULTS: Among 195 patients carrying the c.482G > A variant, 125 (64.1%) cases were diagnosed by newborn screening (NBS), 60 (30.8%) cases were detected due to disease onset, and 10 (5.1%) cases were identified from sibling diagnoses. One hundred and seventeen (93.6%) individuals who were diagnosed by NBS, and nine patients who came from sibling diagnoses remained asymptomatic in this study. From 69 symptomatic patients of the c.482G > A group, more patients presented with later onset, and the top six common clinical symptoms at disease onset were developmental delay (59.4%), lower limb weakness and poor exercise tolerance (50.7%), cognitive decline (37.7%), gait instability and abnormal posture (36.2%), seizures (26.1%), and psychiatric and behavioral disturbances (24.6%). In the 159 symptomatic patients lacking c.482G > A variants, the most frequently observed clinical manifestations at disease onset included developmental delay (81.8%), lethargy and feeding difficulty (62.9%), lower limb weakness and poor exercise tolerance (54.7%), prolonged neonatal jaundice (51.6%), vomiting (47.2%), and seizures (32.7%). Before treatment, the levels of blood propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, and homocysteine in the c.482G > A group were significantly lower (P < 0.05) than those in the non-c.482G > A group, while the concentration of urinary methylmalonic acid was slightly lower (P > 0.05). The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels (P < 0.05). In patients carrying the c.482G > A variant compared with the non-c.428G > A group, there were markedly lower rates of mortality (0.5% vs. 2.0%) and developmental delay (20.5% vs. 65.5%). When compared with individuals diagnosed due to disease onset, those identified through NBS in either group exhibited a reduced proportion of disease onset (6.7% vs. 100% in the c.482G > A group, 54.4% vs. 100% in the non-c.482G > A group), lower mortality (0.0% vs. 1.7% in the c.482G > A group, 0.0% vs. 3.6% in the non-c.482G > A group), and had a higher percentage of patients exhibiting normal psychomotor and language development (99.3% vs. 33.3% in the c.482G > A group, 58.9% vs. 10.9% in the non-c.482G > A group). CONCLUSIONS: The c.482G > A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease. Patients with this mutation tend to have a relatively better response to hydroxocobalamin, better metabolic control, and more favorable neurological outcomes. NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis, resulting in favorable clinical outcomes. Video Abstract (MP4 136794 kb).

Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases.

BACKGROUND: Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut-type MMA in Chinese patients. METHODS: We recruited 365 patients with mut-type MMA; investigated their disease onset, newborn screening (NBS) status, biochemical metabolite levels, gene variations and prognosis; and explored the relationship between phenotype and genotype. RESULTS: There were 152 patients diagnosed by tandem mass spectrometry (MS/MS) expanded NBS, 209 patients diagnosed because of disease onset without NBS and 4 cases diagnosed because of sibling diagnosis. The median age of onset was 15 days old, with a variety of symptoms without specificity. Urinary levels of methylmalonic acid and methylcitric acid (MCA) decreased after treatment. Regarding the prognosis, among the 152 patients with NBS, 50.6% were healthy, 30.3% had neurocognitive impairment and/or movement disorders and 13.8% died. Among the 209 patients without NBS, 15.3% were healthy, 45.9% had neurocognitive impairment and/or movement disorders and 33.0% died. In total, 179 variants were detected in the MMUT gene, including 52 novel variations. c.729_730insTT, c.1106G>A, c.323G>A, c.914T>C and c.1663G>A were the five most frequent variations. The c.1663G>A variation led to a milder phenotype and better prognosis. CONCLUSION: There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis.

In Situ Tumor Vaccine for Lymph Nodes Delivery and Cancer Therapy Based on Small Size Nanoadjuvant.

Tumor vaccine is a promising cancer treatment modality, however, the convenient antigens loading in vivo and efficient delivery of vaccines to lymph nodes (LNs) still remain a formidable challenge. Herein, an in situ nanovaccine strategy targeting LNs to induce powerful antitumor immune responses by converting the primary tumor into whole-cell antigens and then delivering these antigens and nanoadjuvants simultaneously to LNs is proposed. The in situ nanovaccine is based on a hydrogel system, which loaded with doxorubicin (DOX) and nanoadjuvant CpG-P-ss-M. The gel system exhibits ROS-responsive release of DOX and CpG-P-ss-M, generating abundant in situ storage of whole-cell tumor antigens. CpG-P-ss-M adsorbs tumor antigens through the positive surface charge and achieves charge reversal, forming small-sized and negatively charged tumor vaccines in situ, which are then primed to LNs. Eventually, the tumor vaccine promotes antigens uptake by dendritic cells (DCs), maturation of DCs, and proliferation of T cells. Moreover, the vaccine combined with anti-CTLA4 antibody and losartan inhibits tumor growth by 50%, significantly increasing the percentage of splenic cytotoxic T cells (CTLs), and generating tumor-specific immune responses. Overall, the treatment effectively inhibits primary tumor growth and induces tumor-specific immune response. This study provides a scalable strategy for in situ tumor vaccination.

SGRT-based DIBH radiotherapy practice for right-sided breast cancer combined with RNI: A retrospective study on dosimetry and setup accuracy.

BACKGROUND: We retrospectively studied the dosimetry and setup accuracy of deep inspiration breath-hold (DIBH) radiotherapy in right-sided breast cancer patients with regional nodal irradiation (RNI) who had completed treatment based on surface-guided radiotherapy (SGRT) technology by Sentinel/Catalyst system, aiming to clarify the clinical application value and related issues. METHODS: Dosimetric indicators of four organs at risk (OARs), namely the heart, right coronary artery (RCA), right lung, and liver, were compared on the premise that the planning target volume met dose-volume prescription requirements. Meanwhile, the patients were divided into the edge of the xiphoid process (EXP), sternum middle (SM), and left breast wall (LBW) groups according to different positions of respiratory gating primary points. The CBCT setup error data of the three groups were contrasted for the treatment accuracy study, and the effects of different gating window heights on the right lung volume increases were compared among the three groups. RESULTS: Compared with free breath (FB), DIBH reduced the maximum dose of heart and RCA by 739.3 ± 571.2 cGy and 509.8 ± 403.8 cGy, respectively (p < 0.05). The liver changed the most in terms of the mean dose (916.9 ± 318.9 cGy to 281.2 ± 150.3 cGy, p < 0.05). The setup error of the EXP group in the anterior-posterior (AP) direction was 3.6 ± 4.5 mm, which is the highest among the three groups. The right lung volume increases in the EXP, SM, and LBW groups were 72.3%, 69.9%, and 67.2%, respectively (p = 0.08), and the corresponding breath-holding heights were 13.5 ± 3.7 mm, 10.3 ± 2.4 mm, and 9.6 ± 2.8 mm, respectively (p < 0.05). CONCLUSIONS: SGRT-based DIBH radiotherapy can better protect the four OARs of right-sided breast cancer patients with RNI. Different respiratory gating primary points have different setup accuracy and breath-hold height.

Metal-phenolic networks with ferroptosis to deliver NIR-responsive CO for synergistic therapy.

As an endogenous gasotransmitter, CO has achieved tremendous advances in cancer treatment through selectively killing cancer cells. However, the application of CO in tumor immunotherapy has not been reported and the tumor targeting delivery is still a tremendous challenge. Herein, thermosensitive boronic acid group-containing CO prodrug was synthesized and fabricated with tannic acid (TA) and iron (Fe) to form metal-phenolic networks, and then loaded with near-infrared (NIR) photothermal agent IR820 to form FeCO-IR820@FeIIITA for combinational therapy of CO and photothermal therapy. Ferroptosis can also be enhanced due to the Fe3+ incorporation. After TA reduced Fe3+ into Fe2+, Fe2+ might lead to intracellular Fenton reaction. Furthermore, in combination with CTLA-4 blockade immunotherapy, FeCO-IR820@FeIIITA remarkably inhibited breast tumor growth, suppressed the lung metastasis and improved the antitumor immune response. To summarize, FeCO-IR820@FeIIITA provides a potential novel option for CO/photothermal/immune synergistic therapy with enhanced ferroptosis through simple compositions and facile synthesis process.

Privacy-preserving local analysis of digital trace data: A proof-of-concept.

We present PORT, a software platform for local data extraction and analysis of digital trace data. While digital trace data hold huge potential for social-scientific discovery, their most useful parts have been unattainable for scientists because of privacy concerns and prohibitive access to application programming interfaces. Recently, a workflow was introduced allowing citizens to donate their digital traces to scientists. In this workflow, citizens' digital traces are processed locally on their machines before providing informed consent to share a subset of the data with researchers. In this paper, we present the newly developed software PORT that implements the local processing part of this workflow, protecting privacy by shielding sensitive data from outside observers, including the researchers themselves. When using PORT, researchers can tailor the local processing procedure suitable to the data download package and research question. Thus, PORT enables a host of potential applications of social data science to hitherto unobtainable data.

The Follow-Up of Chinese Patients in cblC Type Methylmalonic Acidemia Identified Through Expanded Newborn Screening.

Objective: The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual. Methods: A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. We collected a large cohort of 538 patients and investigated their clinical data in detail, including disease onset, biochemical metabolites, and gene variation, and explored different factors on the prognosis. Results: The long-term outcomes of all patients were evaluated, representing 44.6% for poor outcomes. In our comparison of patients with already occurring clinical signs before treatment to asymptomatic ones, the incidence of intellectual impairment, movement disorders, ocular complications, hydrocephalus, and death were significantly different (p < 0.01). The presence of disease onset [Odd ratio (OR) 12.39, 95% CI 5.15-29.81; p = 0.000], variants of c.609G>A (OR 2.55, 95% CI 1.49-4.35; p = 0.001), and c.567dupT (OR 2.28, 95% CI 1.03-5.05; p = 0.042) were independently associated with poor outcomes, especially for neurodevelopmental deterioration. Conclusion: NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have protective effects on the prognosis of infants with cblC defect.

Associations of Maternal Adverse Childhood Experiences with Behavioral Problems in Preschool Children.

Investigations have found maternal adverse childhood experiences (ACEs) cause an intergenerational danger to their children's health. However, no study has investigated the effects of maternal ACEs on behavioral problems of preschool children in China and gender differences on these effects. This paper aims to investigate the role of maternal ACEs on behavioral problems of preschool children in China and explore gender differences as related to these behavioral problems. Stratified cluster sampling method was used to select 7318 preschool children from 12 districts in Hefei city, China. A questionnaire survey was conducted to collect information on maternal exposure to ACEs and Conners' Parent Rating Scales. Logistic regression was used to analyze the relationship between maternal ACEs and children's behavioral problems. The prevalence of behavioral problems in preschool children was 16.0%, while it was higher among girls (18.4%) than boys (13.92%) (χ2 = 27.979, p < 0.001). The rate of behavioral problems in children in the group of mothers with ACEs was higher than those without ACEs (all p < 0.05). Maternal ACEs were associated with increased risk of the behavior problems in preschool children (adjusted OR 2.91, 95% CI 2.45-3.45), and no gender difference (in girls 3.01, 2.38-3.81, in boys 2.79, 2.17-3.58, respectively) was found. Maternal ACEs were associated with increased risk of each type of the behavioral problems of preschool children, except that maternal emotional neglect was not associated with psycho-physical problems, impulse-activities, and anxiety. The only gender differences found were higher conduct problems related to maternal emotional abuse and ACEs and higher anxiety related to maternal physical abuse and community violence in girls compared with boys. Mothers exposured to ACEs are more likely to have children with behavioral health problems in preschool period. Further research is needed to explore the mechanisms by which maternal ACEs influence children's behavioral problems.

Different mutations in the MMUT gene are associated with the effect of vitamin B12 in a cohort of 266 Chinese patients with mut-type methylmalonic acidemia: A retrospective study.

BACKGROUND: To summarize the relationship between different MMUT gene mutations and the response to vitamin B12 in MMA. METHODS: This was a retrospective study of patients diagnosed with mut-type MMA. All patients with mut-type MMA were tested for responsiveness to vitamin B12. RESULTS: There were 81, 27, and 158 patients in the completely responsive, partially responsive, and nonresponsive groups, respectively, and the proportions of symptom occurrence were 30/81 (37.0%), 21/27 (77.8%), and 131/158 (82.9%), respectively (p < .001). The median levels of posttreatment propionyl carnitine (C3), C3/acetyl carnitine (C2) ratio in the blood, and methylmalonic acid in the urine were all lower than pretreatment, and the median level of C3/C2 ratio in the completely responsive group was within the normal range. In 266 patients, 144 different mutations in the MMUT gene were identified. Patients with the mutations of c.1663G>A, c.2080C>T, c.1880A>G, c.1208G>A, etc. were completely responsive and with the mutations of c.1741C>T, c.1630_1631GG>TA, c.599T>C, etc. were partially responsive. The proportions of healthy/developmental delay outcomes in the three groups were 63.0%/23.5%, 33.3%/40.7%, and 13.3%/60.1%, respectively (p < .001). CONCLUSION: Different mutations in the MMUT gene are associated with the effect of vitamin B12 treatment.

C4OH is a potential newborn screening marker-a multicenter retrospective study of patients with beta-ketothiolase deficiency in China.

BACKGROUND: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. RESULTS: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. CONCLUSION: This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients.

BACKGROUND: Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype. METHODS: Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. RESULTS: Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients. CONCLUSION: Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

Accuracy of multitarget indirect enzyme-linked immunoassay assay for detection of tuberculosis antibody.

BACKGROUND: Diagnosis of tuberculosis (TB) is still difficult. The development of rapid and sensitive laboratory tools for the diagnosis of tuberculosis is a priority. This study aimed to develop an indirect enzyme-linked immunoassay (ELISA) assay for detection of TB antibody and explore its diagnostic value in patients with pulmonary tuberculosis (PTB) via a multi-center clinical evaluation. METHODS: The specific antigen, fusion antigen, and specific antibody peptide were obtained using molecular cloning and phage peptide library screening. An indirect ELISA assay was developed using multiple target materials. Further, the assay was validated in six institutions with clinically confirmed TB patients, non-TB patients with pulmonary disease, and healthy controls as research subjects. RESULTS: An indirect ELISA assay was developed with 16 kD antigen, 11,488 (CFP10-MPT48-TB8.4) fusion antigen, and TB18 and pl2 as target antigens against TB antibody. The results of this multicenter study showed that the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of the assay were 48.25% [95% confidence interval (CI): 45.5-51.1%], 92.20% (95% CI: 90.7-93.5%) and 0.724 (95% CI: 0.707-0.741), respectively, and the cut-off value was 0.119. According to the meta-analysis, the combined ROC was 0.736 (95% CI: 0.692-0.779), I2=83.73%. The sensitivity of the sputum-positive PTB group (culture or smear positive) was 58.75% (95% CI: 52.96-65.00%); the sensitivity in sputum-negative group (culture or smear negative) was 37.38% (95% CI: 32.71-42.52%), respectively; the sensitivity of the sputum-positive group was significantly higher than that of sputum-negative group (OR =1.57, 95% CI: 1.29-1.92, P<0.001). CONCLUSIONS: Multitarget indirect ELISA assay based on specific-TB antigen, fusion antigen, and antibody peptide is of value for the diagnosis of PTB and can be used as an auxiliary rapid diagnostic tool to improve the sensitivity of sputum-negative TB.

The 15° reverse Trendelenburg position can improve visualization without impacting cerebral oxygenation in endoscopic sinus surgery-A prospective, randomized study.

BACKGROUND: In this study we compared intraoperative bleeding and regional cerebral oxygenation in patients with different degrees of the reverse Trendelenburg position (RTP) during endoscopic sinus surgery (ESS). METHODS: In total, 120 patients with chronic rhinosinusitis treated by ESS were randomly assigned to the following 4 groups: a horizontal position (HP) group, and 5°, 10°, and 15° RTP (5-RTP, 10-RTP, and 15-RTP, respectively) groups. The primary outcome was the Boezaart grading scale (BS). The cerebral oxygen saturation (ScO2 ), total blood loss, numerical rating scale (NRS) scores, and complications were also recorded. RESULTS: The median BS values in the HP, 5-RTP, 10-RTP, and 15-RTP groups were 2.0, 2.0, 2.1, and 1.7, respectively. Multiple pairwise comparisons of the BS showed significant differences between the 15-RTP group and the other 3 groups (HP, 5-RTP, and 10-RTP). Regarding the NRS and bleeding rate, significant differences were found between the HP and 15-RTP groups. No difference was found in ScO2 among the 4 groups, and no cerebral desaturation events occurred in any group. No complications, including vital organ (heart, brain, and kidney) dysfunction problems, were reported in this study during hospitalization. CONCLUSION: Compared with HP, 5-RTP, and 10-RTP, 15-RTP can improve visual clarity during ESS, and ScO2 is not affected by the degree of RTP. No cerebral deoxygenation or vital organ dysfunction was observed in this study. Therefore, we recommend 15-RTP with moderate deliberate hypotension for ESS.

Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4.

Radiation enteritis is one of the most common side effects of ionizing radiation in patients with pelvic cancers. Increasing amounts of evidence indicate that pro-inflammatory responses significantly contribute to the development of radiation enteritis. In this study, we investigated the association between T regulatory (Treg) cells and the risk of developing radiation enteritis in cervical cancer patients. The following observations were made. First, the frequencies of CD25hiFoxp3+ Treg cells were significantly lower in patients with radiation enteritis than in both healthy subjects and cervical cancer patients without radiation enteritis. Also, patients with the more severe grade 3 enteritis presented significantly lower Treg levels than patients with the more common grade 1 enteritis. Second, the expression of several molecules associated with Treg function, including CTLA-4, IL-10, TGF-ß, and perforin, was significantly lower in patients with radiation enteritis than in healthy subjects. In patients without radiation enteritis, however, only CTLA-4, but not other Treg-associated suppressive molecules, was reduced in Treg cells. Third, Treg cells can markedly suppress CD8 T cell proliferation, but in patients with radiation enteritis, this function of Treg cells was significantly impaired, in a manner that was associated with lower CTLA-4 expression. Overall, these data suggest that the frequency and function of Treg cells is negatively associated with the risk of developing enteritis following radiation. In clinical practice, the characteristics of Treg cells may be considered to evaluate the risk of developing enteritis if the cancer patient is receiving ionizing radiation.

Combining newborn metabolic and genetic screening for neonatal intrahepatic cholestasis caused by citrin deficiency.

To evaluate the feasibility of incorporating genetic screening for neonatal intrahepatic cholestasis, caused by citrin deficiency (NICCD), into the current newborn screening (NBS) program. We designed a high-throughput iPLEX genotyping assay to detect 28 SLC25A13 mutations in the Chinese population. From March 2018 to June 2018, 237 630 newborns were screened by tandem mass spectrometry at six hospitals. Newborns with citrulline levels between 1/2 cutoff and cutoff values of the upper limit were recruited for genetic screening using the newly developed assay. The sensitivity and specificity of the iPLEX genotyping assay both reached 100% in clinical practice. Overall, 29 364 (12.4%) newborns received further genetic screening. Five patients with conclusive genotypes were successfully identified. The most common SLC25A13 mutation was c.851_854del, with an allele frequency of 60%. In total, 658 individuals with one mutant allele were identified as carriers. Eighteen different mutations were observed, yielding a carrier rate of 1/45. Notably, Quanzhou in southern China had a carrier rate of up to 1/28, whereas Jining in northern China had a carrier rate higher than that of other southern and border cities. The high throughput iPLEX genotyping assay is an effective and reliable approach for NICCD genotyping. The combined genetic screening could identify an additional subgroup of patients with NICCD, undetectable by conventional NBS. Therefore, this study demonstrates the viability of incorporating genetic screening for NICCD into the current NBS program.

Newborn Screening for Spinal Muscular Atrophy in China Using DNA Mass Spectrometry.

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disorder and the leading genetic cause of infant mortality. Early detection of SMA through newborn screening (NBS) is essential to selecting pre-symptomatic treatment and ensuring optimal outcome, as well as, prompting the urgent need for effective screening methods. This study aimed to determine the feasibility of applying an Agena iPLEX SMA assay in NBS for SMA in China. Methods: We developed an Agena iPLEX SMA assay based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and evaluated the performance of this assay through assessment of 167 previously-genotyped samples. Then we conducted a pilot study to apply this assay for SMA NBS. The SMN1 and SMN2 copy number of screen-positive patients were determined by multiplex ligation-dependent probe amplification analysis. Results: The sensitivity and specificity of the Agena iPLEX SMA assay were both 100%. Three patients with homozygous SMN1 deletion were successfully identified and conformed by multiplex ligation-dependent probe amplification analysis. Two patients had two SMN2 copies, which was correlated with severe SMA type I phenotype; both of them exhibited neurogenic lesion and with decreased muscle power. Another patient with four SMN2 copies, whose genotype correlated with milder SMA type III or IV phenotype, had normal growth and development without clinical symptoms. Conclusions: The Agena iPLEX SMA assay is an effective and reliable approach for population-based SMA NBS. The first large-scale pilot study using this assay in the Mainland of China showed that large-scale implementation of population-based NBS for SMA is feasible.